Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle
Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle
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DOI：
10.1111/j.1440-1681.2005.04176.x
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发表时间：
2005-03-01
影响因子：
2.9
通讯作者：
Kumagai, S
中科院分区：
文献类型：
--
作者：
Suwa, M;Nakano, H;Kumagai, S
1.本研究旨在通过给大鼠注射钙调神经磷酸酶抑制剂环孢素A(CsA)来研究钙调神经磷酸酶在肌肉代谢成分中的作用。雄性Wistar大鼠分为CsA治疗组(CT)和赋形剂治疗组(VT)。大鼠皮下注射环孢素A，每天25 mg/kg体重，连续给药10d。观察慢抽动比目鱼肌和快抽动趾长伸肌(EDL)肌酶活性及葡萄糖转运体(GLUT)-4和单羧酸转运体(MCT)-1和MCT-4蛋白的变化。CT组比目鱼肌中MCT-1和MCT-4蛋白表达显著增加，而EDL肌中MCT-1和MCT-4蛋白表达无明显变化。CT组比目鱼肌中己糖激酶、丙酮酸激酶和乳酸脱氢酶的活性也显著升高，而EDL肌中的酶活性未见类似的升高。CsA处理对比目鱼肌和EDL肌的柠檬酸合成酶或苹果酸脱氢酶活性和GLUT-4蛋白含量均没有影响。这些结果似乎表明，钙调神经磷酸酶负向调节葡萄糖/乳酸代谢的成分，除了GLUT-4，特别是在慢抽动肌肉中。
1. The present study was designed to examine the role of calcineurin in muscle metabolic components by the administration of the specific calcineurin inhibitor cyclosporine A (CsA) to rats.2. Male Wistar rats were divided into either a CsA-treated group (CT) or a vehicle-treated group (VT). Cyclosporine A was administered subcutaneously to rats at a rate of 25 mg/kg bodyweight per day for 10 successive days. Thereafter, changes in muscle enzyme activities and glucose transporter (GLUT)-4 and monocarboxylate transporter (MCT)-1 and MCT-4 proteins in the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles were examined.3. There was a significant increase in MCT-1 and MCT-4 proteins in the soleus muscle in the CT group, but not in the EDL muscle. The activities of hexokinase, pyruvate kinase and lactate dehydrogenase in the soleus muscle also increased significantly in the CT group, but a similar increase in enzyme activity was not seen in EDL muscle. The activities of citrate synthase or malate dehydrogenase and the GLUT-4 protein content were not altered by CsA treatment in either the soleus or EDL muscles.4. These results seem to imply that calcineurin negatively regulates the components of glucose/lactate metabolism, except for GLUT-4, especially in slow-twitch muscle.